Females of the Southern House mosquito, Culex quinquefasciatus, rely on environmental cues, also known as oviposition attractants (OAs), to locate suitable sites for laying eggs. Their antennae are endowed with hair-like structures called sensilla. We have already identified three types of sensilla on the antennae of the Southern House mosquito that detect OAs. This research is aimed at testing the hypothesis that both odorant-binding proteins (OBPs) and odorant receptors (ORs), which are harbored in these sensilla, are essential for reception of OAs. Affinity of OBPs mined from the Culex genome towards a small set of known OAs will be measured. Function of OBPs with high affinity for OAs will be further evaluated by RNAi and electrophysiology to unambiguously identify those involved in OA reception. Candidate ORs identified from the genome will be expressed in the Xenopus oocyte system and tested against a panel of odorants, which include known OAs. A comparison of their response profiles with the profiles obtained from the mosquito antennae in our preliminary studies will allow identification of receptors and their localization in the OA-detecting sensilla. The olfactory proteins involved in OA reception will be used to screen a library of natural products to prospect for a second generation of OAs. Compounds already identified in preliminary studies and those derived from the above-mentioned molecular approaches will be tested by indoor behavioral studies and ultimately in the field. That way we plan to develop better OAs for monitoring and surveillance as well as to pave the way for novel environmentally friendly strategies for controlling Culex mosquito populations. PUBLIC HEALTH RELEVANCE: Mosquitoes in the genus Culex are vectors of pathogens causing human diseases throughout the world, including filariasis, various types of encephalitis, and in the United States they spread West Nile Virus while feeding on birds and humans. Vector surveillance and monitoring of Culex populations are reliant on chemical cues to attract gravid females searching for oviposition sites, but current trapping technologies need improvements, particularly the development of better oviposition attractants (OAs). This research is aimed at advancing our knowledge of mosquito olfaction as well as to develop a second generation of OAs, which may be used for trapping, surveillance and possibly green chemistry for controlling mosquito populations.